tert-Butylhydroperoxide induces apoptosis in RAW264.7 macrophages via a mitochondria-mediated signaling pathway

Abstract

Macrophage apoptosis occurs throughout all stages of atherosclerosis, mainly induced by oxidized low density lipoproteins (Ox LDLs), leading to the formation of necrotic cores. Nevertheless, the mechanism of macrophage apoptosis induced by Ox LDLs is not yet clearly understood. In this study, a model of RAW264.7 macrophages exposed to an Ox LDL analogue, i.e. tert-butylhydroperoxide (t-BHP), was established. We thoroughly evaluated the viability and apoptosis of RAW264.7 cells treated with t-BHP at different time intervals. t-BHP treatment decreases the viability of RAW264.7 cells in a dose- and time-dependent manner (IC₅₀: 400 μM) and also induces a loss of the mitochondrial membrane potential (MMP) in RAW264.7 cells. Moreover, the activation of Bid, up-regulation of Bcl-2, and down-regulation of Bax, as well as the proteolysis of pro-caspase 3 and cleavage of PARP, were all also observed in t-BHP treated RAW264.7 cells. Finally, we concluded that t-BHP induces the apoptosis of macrophages via a mitochondria-mediated signaling pathway.